The proposed work investigates (I) interrelationships between the reproductive endocrine system and control over body temperature in hibernating mammals, and (II) mechanisms by which arctic ground squirrels, (Spermophilus parryii), spontaneously adopt subzero body temperatures without freezing. Specific aims related to reproductive function and hibernation include: (1) characterizing plasma gonadotropin and steroid hormone levels during the spontaneous termination of hibernation; (2) testing for central nervous system sensitivity to androgen inhibition of hypothermia; and (3) determining whether plasma steroid hormonebinding proteins prevent such inhibition during the hibernation season. Specific aims related to investigating mechanisms of mammalian freeze resistance include: (1) determining the limits to subzero temperature tolerance in arctic ground squirrels and testing blood sampled from freeze-resisting animals for the presence of antifreeze substances and cryoprotectants; (2) measuring seasonal changes in plasma and tissue supercooling points (crystallization temperatures), as well as changes in serum proteins and lipoproteins; (3) identifying potential ice nucleation factors in blood and determining whether ground squirrels eliminate or mask these in order to avoid freezing; (4) artificially inoculating freezing in supercooled animals to investigate mechanisms of freeze defense; and (5) examining the role of nonshivering thermogenesis in stabilizing subzero hypothermia. These experiments should elucidate novel functional relationships between the reproductive endocrine system, plasma binding proteins, and central nervous system control over body temperature in mammals. They address the question of how reproductive recrudescence begins during the constant darkness and periodic low body temperatures of hibernation. Other experiments investigate important basic questions about apparently unique mechanisms of freeze resistance in mammals, answers to which may relate to the use of cryopreservation of transplant organs and mammalian tolerance to severe hypothermia.